For patients with advanced HER2-positive breast cancer, few effective treatment options are currently available. The monarcHER trial studied the safety and efficacy of several drugs, including non-chemotherapy options, to address this unmet need.
More than 200 patients were enrolled and assigned to one of three groups. The three treatment options included abemaciclib, trastuzumab, and fulvestrant, abemaciclib and trastuzumab, or chemotherapy and trastuzumab. Of the patients enrolled, half had received two to three previous systemic therapies, while the other half had more than three. The median for all three groups in the intent-to-treat population was four (IQR 3-5).
According to results published in The Lancet, the median follow-up was 19 months, with authors noting that the trial met its primary endpoint of median progression-free survival between the first group (8.3 months, 95% CI 5.9-12.6) and third group (5.7 months, 5.4-7.0; HR 0.67 [95% CI 0.45-1.00.]; p=0.051.) The authors also noted there was no difference between median progression-free survival in the second group (5.7 months, 95% CI 4.2-7.2) and the third group (HR 0.94 [0.64-1.38] p =0.77).
The most common grade 3-4 treatment-emergent adverse event in the three groups was neutropenia. The most common adverse events in the first group were pyrexia, diarrhea, urinary tract infection, and acute kidney injury. The most common events in the second group included diarrhea and pneumonitis, and neutropenia and pleural effusion were the most commonly reported events in the third group. One patient in the second group died due to pulmonary fibrosis, and one in the third group died of febrile neutropenia.
In the article in The Lancet, the authors said they believed their trial was the first to have positive results with a CDK4 and CDK6 inhibitor in combination with fulvestrant and trastuzumab compared to standard chemotherapy and trastuzumab.
“The endocrine combination of abemaciclib plus fulvestrant and trastuzumab showed significant improvements in both progression-free survival and overall response compared with chemotherapy plus trastuzumab and was generally well tolerated,” the authors said. “The current study is noteworthy as it directly compared an endocrine-based regimen with standard-of-care chemotherapy in combination with trastuzumab, potentially offering a chemotherapy sparing treatment option.”
The study authors noted that the “treatment landscape for patients with HER2-positive advanced breast cancer is rapidly evolving.” They said the addition of new medications to the armamentarium and the ability to combine them has significantly impacted the ability to treat patients. They also said the ability to go outside of chemotherapy for treatment could be beneficial and attractive to both patients and providers.
“Even in a rapidly changing environment with multiple new molecules entering the market, there remains an unmet need for patients with advanced disease who might wish to have a chemotherapy-free option available,” the authors said.
